Myo-Inositol (PCOS)

AIMS: Polycystic ovary syndrome (PCOS) is a common endocrine disorder in reproductive-age women, associated with insulin resistance, hyperandrogenism, and menstrual irregularities. Nutraceutical interventions-bioactive compounds derived from foods or supplements that provide health benefits beyond basic nutrition-may support conventional therapy. This study aimed to systematically evaluate the effects of nutraceutical interventions on reproductive and metabolic outcomes in PCOS. MATERIALS AND METHODS: This systematic review and meta-analysis was registered in PROSPERO (CRD42024521879) and followed PRISMA 2020. Searches were performed in PubMed, Embase, Cochrane Library, Web of Science, and regional databases (January 2013-December 2024) and included 78 eligible studies. Eligible randomized and quasi-experimental studies assessed nutraceuticals such as vitamin D, inositol, and quercetin. Risk of bias was evaluated with standardized tools; certainty of evidence was graded by GRADE. RESULTS: Seventy-eight studies met inclusion criteria. Nutraceutical interventions significantly reduced fasting insulin (MD = -2.14 μIU/mL; 95% CI -3.12 to -1.16) and luteinizing hormone (MD = -1.34 mIU/mL; 95% CI -2.10 to -0.58) and increased sex-hormone-binding globulin (MD = +3.72 nmol/L; 95% CI 1.35 to 6.09). Vitamin D supplementation showed the strongest metabolic and hormonal improvements. Results for ovarian follicle count and menstrual bleeding were inconsistent. CONCLUSIONS: Nutraceutical interventions targeting metabolic and hormonal regulation may complement lifestyle therapy in women with PCOS. Interpretation is limited by study heterogeneity and variable methodological quality. No external funding was received. © 2025 John Wiley & Sons Ltd.

BACKGROUND: Nutritional supplements are known to ameliorate polycystic ovary syndrome (PCOS) and have been shown to modulate endocrine and metabolic markers, oxidative stress markers and inflammatory biomarkers in patients with PCOS. A variety of nutritional supplements have been applied in clinics, but a more comprehensive ranking of their efficacy has not yet been investigated. OBJECTIVES: To assess the comparative effectiveness of nutritional supplements in women with PCOS. METHODS: A systematic search was conducted across PubMed, EMBASE, Web of Science, and the Cochrane Library for randomized controlled trials (RCTs) that met the inclusion criteria up to October 12, 2023. We performed a network meta-analysis (NMA) to evaluate the effectiveness of various nutritional supplements on different indicators of PCOS by synthesizing both direct and indirect evidence from the trials. RESULTS: Seventy-nine RCTs involving 5,501 participants were enrolled in the NMA. It suggested that chromium was notably effective in improving follicle-stimulating hormone levels, total antioxidant capacity, and very low-density lipoprotein levels. Soy isoflavones were more beneficial for enhancing glutathione levels and reducing malondialdehyde levels. Inositol significantly decreased total cholesterol and triglyceride levels, while curcumin was most effective in improving low-density and high-density lipoprotein cholesterol levels. Additionally, Omega-3 was superior in reducing homeostatic model assessment of insulin resistance levels. No significant differences were observed in total testosterone, sex hormone-binding globulin, dehydroepiandrosterone, high-sensitivity C-reactive protein, and plasma nitric oxide levels between the supplements and placebo. CONCLUSIONS: Chromium, inositol, and Omega-3 were found to be beneficial for improving lipid profile. For improving obesity, sex hormone levels, inflammatory factors and oxidative stress indicators of PCOS patients, carnitine, chromium, and soy isoflavones are effective options, respectively. These findings confirm that nutritional supplements can effectively alleviate PCOS symptoms, potentially providing valuable guidance for the cli

OBJECTIVE: There has been substantial research conducted recently on the effect of myo-inositol (MI) on human reproduction. However, it still remains ambiguous about the therapeutic efficacy of MI in infertile women undergoing in vitro fertilization embryo transfer (IVF-ET). This systematic review and meta-analysis was carried out to investigate the efficacy of MI on IVF outcomes. METHODS: Literatures were searched in the PubMed, Web of Science, Cochrane Library, ScienceDirect and Wanfang databases. The methodological quality was assessed using the Cochrane Risk of Bias tool. Data were pooled using a random- or fixed-effects model according to study heterogeneity. The results are expressed as odds ratio (OR) or mean difference (MD) with 95% confidence intervals (CIs). Heterogeneity was measured by the I2 statistic. The protocol was prospectively registered with PROSPERO (CRD42024582149). RESULTS: Eleven eligible studies with 981 participants reported the IVF outcomes of the MI group versus the control group. The synthesis results showed that the metaphase II (MII) oocyte rate was higher in the MI group than in the control group (OR 1.55, 95% CI 1.04-2.31, P=0.03). For polycystic ovary syndrome (PCOS) women, as well as non-obese PCOS women, a statistically significant improvement in MII oocyte rate were assumed after taking MI (OR 1.97, 95% CI 1.20-3.25, P<0.01; OR 1.92, 95% CI 1.09-3.37, P=0.02) while there is no statistically significant advancement showed in the poor ovary responder (POR) women(OR 0.97, 95% CI 0.35-2.68, P=0.95). The fertilization rate was higher in the MI group than in the control group (OR 1.62, 95% CI 1.21-2.16, P<0.01), for PCOS, non-obese PCOS and POR women (OR 1.59, 95% CI 1.16-2.18, P<0.01; OR 1.87, 95% CI 1.52-2.31, P<0.01; OR 2.42, 95% CI 1.48-3.95, P<0.01). CONCLUSIONS: Our results suggest that MI supplementation improves the MII oocyte rate and the fertilization rate. More high-grade evidence from prospective randomized studies is warranted. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024582149.

OBJECTIVE: To explore the comparative effectiveness of nutritional supplements in improving glycolipid metabolism and endocrine function in patients with polycystic ovary syndrome (PCOS). METHOD: Randomized controlled clinical trials on the effects of nutritional supplements in PCOS patients were searched in PubMed, Embase, Cochrane Library, and Web of Science from their establishments to March 15, 2023. Then, literature screening, data extraction, and network meta-analysis were performed. This study was registered at PROSPERO (registration number CRD 42023441257). RESULT: Forty-one articles involving 2,362 patients were included in this study. The network meta-analysis showed that carnitine, inositol, and probiotics reduced body weight and body mass index (BMI) compared to placebo, and carnitine outperformed the other supplements (SUCRAs: 96.04%, 97.73%, respectively). Omega-3 lowered fasting blood glucose (FBG) (SUCRAs: 93.53%), and chromium reduced fasting insulin (FINS) (SUCRAs: 72.90%); both were superior to placebo in improving insulin resistance index (HOMA-IR), and chromium was more effective than Omega-3 (SUCRAs: 79.99%). Selenium was potent in raising the quantitative insulin sensitivity index (QUICKI) (SUCRAs: 87.92%). Coenzyme Q10 was the most effective in reducing triglycerides (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels (SUCRAs: 87.71%, 98.78%, and 98.70%, respectively). Chromium and probiotics decreased TG levels, while chromium and vitamin D decreased TC levels. No significant differences were observed in high-density lipoprotein cholesterol (HDL-C), total testosterone (TT), sex-hormone binding globulin (SHBG), and C-reactive protein (CRP) between nutritional supplements and placebo. CONCLUSION: Carnitine was relatively effective in reducing body mass, while chromium, Omega-3, and selenium were beneficial for improving glucose metabolism. Meanwhile, coenzyme Q10 was more efficacious for improving lipid metabolism. However, publication bias may exist, and more high-quality clinical randomized controlled trials are needed. © 2023 Hu et al.

Polycystic ovary syndrome (PCOS) is a common cause of female infertility, affecting 5-10% of women of reproductive age. Many studies have reported improvement in insulin resistance and thereby intracellular glucose uptake after myo-inositol treatment in PCOS patients, but these studies have a small sample size, varying methodology, and outcome analysis. Therefore, we designed a present meta-analysis of randomized controlled trials to explore the effect of myo-inositol supplementation on anthropometric, metabolic, and endocrine outcomes in PCOS patients. Randomized controlled trials assessing the effectiveness of myo-inositol were identified in electronic databases like PubMed, Cochrane, Embase, MEDLINE, CINAHL, and AMED. Listed references and citations of related articles were also screened manually to identify additional studies. Research papers for which full-text copies were not available on scientific databases were procured from respective authors. Thereafter, data were extracted from included studies and analyzed using RevMan 5.3 of the Cochrane Collaboration. A total of 17 randomized controlled trials with 1083 PCOS patients were included in this meta-analysis. Among the 17 trials, 7 trials compared myo-inositol with folic acid, 8 trials compared myo-inositol with metformin, and 2 trials compared myo-inositol with oral contraceptives. No significant improvement in body mass index, waist-to-hip ratio, fasting insulin, fasting glucose, HOMA, LH, FSH, estradiol, sex hormone-binding globulin, dehydroepiandrosterone, and total testosterone levels were observed after myo-inositol treatment in PCOS patients except androstenedione and prolactin levels. Clinically significant improvement was not observed in anthropometric, metabolic, and endocrine outcomes after myo-inositol treatment in PCOS patients. However, heterogeneity between studies was high. © 2022. Society for Reproductive Investigation.

OBJECTIVE: This meta-analysis aims to perform an updated meta-analysis to evaluate myo-inositol (myo-ins) and the classical insulin sensitizer metformin in terms of efficacy and safety for treating women with polycystic ovary syndrome (PCOS). MATERIALS AND METHODS: A comprehensive literature search was performed using PubMed, Web of Science, EMBASE, Cochrane Library, PhRMA Clinical Study Results, Wan Fang, and CNKI databases; the database was searched from inception to June 2021. The random effects model was chosen to synthesize the effect sizes of individual trails. The registration number is CRD42021239786. RESULTS: Nine randomized controlled trials (RCTs) and 612 patients were included in the analysis. Compared with metformin, myo-ins might be more effective in lowering triglycerides (TG) levels (SMD -0.49, 95% CI -0.74 to -0.24, p=0.0001, I2 = 0%) and avoiding side effects (RR=0.14, 95% CI 0.08-0.24, p<0.00001, I2 = 2%), while no significant differences were observed in other relevant indexes, such as total testosterone (TT) and sex-hormone binding globulin (SHBG). CONCLUSIONS: Compared with metformin, the suitable supplemental dosage of myo-ins may be helpful in lowering levels of TG and avoiding adverse events (AEs).

OBJECTIVE: This research evaluated the efficacy of oral nutritional agents including CoQ10, vitamin E, inositols and vitamin D on androgen-associated hormones, glycolipid metabolism and body weight in women with PCOS. METHOD: A multi-database search was performed from inception to December 2020. Using multi-variate random effects method, a NMA was conducted by synthesizing data pooled from RCTs. It was registered with PROSPERO (registration number CRD42021230292). RESULTS: Twenty-three RCTs and 1291 participants were included. Based on NMA, CoQ10, vitamin E, CoQ10 combined with vitamin E, and inositols were successful in decreasing TT as compared with PA; vitamin E was superior to other agents. Vitamin E and inositols were successful in increasing SHBG levels; inositols were stronger than vitamin E. CoQ10 alone or combined with vitamin E, and inositols were successful in decreasing HOMA-IR. Inositols had the best results among included nutraceuticals to ameliorate HOMA-IR, FBG, FINS, TG, TC, and LDL-C and correlated to improvements in BMI. There was no significant difference between the CoQ10 or vitamin E group and the PA group in ameliorating lipid metabolism, and vitamin D had no positive effects in ameliorating hyperandrogenism, BMI, glycolipid metabolism profiles compared with PA. CONCLUSION: For women with PCOS, inositols supplementation have some certain advantages in increasing SHBG and improving glycolipid metabolism when compared with nutraceuticals like CoQ10, vitamin E, vitamin D. Besides, vitamin E may be a better option in reducing TT and increasing SHBG. CoQ10 alone or combined with vitamin E can be helpful in decreasing HOMA-IR as well.

Metformin (MET), the most commonly used insulin sensitizer, is the reference off-label drug for the treatment of polycystic ovary syndrome (PCOS), worldwide. However, its use may be limited mainly by gastrointestinal adverse effects. Myo-inositol (MI), a well-recognized food supplement, also represents an evidence-based treatment for PCOS women, popular in many countries. Our aim is to provide a systematic review of the literature and a meta-analysis which compares these two treatments, for their short-term efficacy and safety in PCOS patients. Systematic review and meta-analysis of randomized clinical trials (RCTs). RCTs were identified from 1994 through 2017 using MEDLINE, Cochrane Library, PubMed, and ResearchGate. Included studies were limited to those one directly comparing MET to MI on several hormones changes. Standardized mean difference (SMD) or risk ratios (RRs) with 95% CIs were calculated. Changes in fasting insulin was the main outcome of measure. Six trials with a total of 355 patients were included. At the end of treatment, no difference between MET and MI was found on fasting insulin (SMD=0.08 µU/ml, 95% CI: -0.31-0.46, p=.697), HOMA index (SMD =0.17, 95% CI: -0.53-0.88, p=.635), testosterone (SMD= -0.01, 95% CI: -0.24-0.21, p=.922), SHBG levels (SMD= -0.50 nmol/l, 95% CI: -1.39-0.38, p=.263) and body mass index (BMI) (SMD= -0.22, 95% CI: -0.60-0.16, p=.265). There was strong evidence of an increased risk of adverse events among women receiving MET compared to those receiving MI (RR =5.17, 95% CI: 2.91-9.17, p<.001). No differences were found in the effect of MET and MI on short-term hormone changes. The better tolerability of MI makes it more acceptable for the recovery of androgenic and metabolic profile in PCOS women.

BACKGROUND: Subfertile women are highly motivated to try different adjunctive therapies to have a baby, and the widespread perception is that dietary supplements such as myo-inositol (MI) and D-chiro-insoitol (DCI) are associated with only benefit, and not with harm. Many fertility clinicians currently prescribe MI for subfertile women with polycystic ovary syndrome (PCOS) as pre-treatment to in vitro fertilisation (IVF) or for ovulation induction; however no high-quality evidence is available to support this practice. This review assessed the evidence for the effectiveness of inositol in subfertile women with a diagnosis of PCOS. OBJECTIVES: To evaluate the effectiveness and safety of oral supplementation of inositol for reproductive outcomes among subfertile women with PCOS who are trying to conceive. SEARCH METHODS: We searched the following databases (to July 2018): Cochrane Gynaecology and Fertility Group (CGFG) Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, and AMED. We also checked reference lists and searched the clinical trials registries. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared any type, dose, or combination of oral inositol versus placebo, no treatment/standard treatment, or treatment with another antioxidant, or with a fertility agent, or with another type of inositol, among subfertile women with PCOS. DATA COLLECTION AND ANALYSIS: Two review authors independently selected eligible studies, extracted data, and assessed risk of bias. The primary outcomes were live birth and adverse effects; secondary outcomes included clinical pregnancy rates and ovulation rates. We pooled studies using a fixed-effect model, and we calculated odds ratios (ORs) with 95% confidence intervals (CIs). We assessed the overall quality of the evidence by applying GRADE criteria. MAIN RESULTS: We included 13 trials involving 1472 subfertile women with PCOS who were receiving myo-inositol as pre-treatment to IVF (11 trials), or during ovulation induction (two trials). These studies compared MI versus placebo, no treatment/standard, melatonin, metformin, clomiphene citrate, or DCI. The evidence was of 'low' to 'very lo

PURPOSE: To evaluate whether oral myo-inositol supplementation (MI) is able to reduce the amount of gonadotropins (GA) and the length of controlled ovarian hyperstimulation (SL) in both Polycystic Ovarian Syndrome (PCOS) and non-PCOS women undergoing in vitro fertilization (IVF). METHODS: We performed a systematic review (PROSPERO ID: CRD42017069439) of randomized controlled trials (RCTs). We searched articles published in English between January 1985 to August 2017, using the combination of the Medical Subject Headings "Inositol" with "Ovulation Induction", "follicle-stimulating hormone, human, with HCG C-terminal peptide", "Reproductive Techniques, Assisted", and "Fertilization in Vitro". We collected data about GA and SL comparing MI to no treatment or D-Chiro-Inositol (DCI) supplementation (controls). A subgroup analysis was performed to evaluate selected outcomes in PCOS and non-PCOS women. RESULTS: We included 8 studies embedding 812 participants. We found a reduction in GA (p < 0.00001) and SL (p = 0.0007) in patients receiving MI with respect to controls. MI was effective in both PCOS (p < 0.00001) and non-PCOS women (p = 0.02) in reducing GA; conversely, MI supplementation decreased the SL only in PCOS women (p < 0.00001). CONCLUSION: During IVF, MI is effective in both PCOS and non-PCOS women in saving gonadotropins, but reduces efficiently SL only in PCOS women.

BACKGROUND: PCOS is a common condition among women of reproductive age, marked by irregular menstrual cycles, hyperandrogenism, and ultrasound abnormalities. Infertility treatments such as metformin and myoinositol often have side effects and low adherence. Ziziphus jujuba has the potential in improving PCOS outcomes, prompting this study to compare its effect on pregnancy rates with conventional therapies. METHODS: This double-blind, randomized trial involved 196 infertile PCOS patients (ages 18-45), with 49 participants in each group. Participants were randomly assigned to four groups: metformin (500 mg daily), myoinositol (2000 mg daily), Ziziphus jujuba hydroalcoholic extract (15 g daily), or placebo (sachet/pill) for 12 weeks. Biochemical (FBG, lipid profile, ALT, AST, ESR, CRP, TyG index) and anthropometric (weight, BMI, waist circumference) measurements were taken pre- and post-study. Ovulation induction with letrozole was performed, and pregnancy occurrence was the primary endpoint, assessed via Beta hCG and ultrasound 6-7 weeks after treatment. RESULTS: No significant differences in pregnancy as primary outcome were found (Ziziphus jujuba: 10, Metformin: 7, Myoinositol: 5, Placebo: 4; p > 0.05). However, significant improvements in cholesterol, TG, HDL cholesterol, and FBG were observed in the Ziziphus jujuba compared to other groups (p < 0.05). CONCLUSION: The Ziziphus jujuba extract demonstrated significant improvements in FBG levels, lipid profiles, and insulin resistance; however, it did not significantly increase pregnancy occurrence compared to metformin, and myoinositol. No serious adverse effects were observed, with only one participant reporting mild constipation. These findings suggest that while Ziziphus jujuba shows promise in metabolic management of PCOS, its efficacy in enhancing fertility outcomes requires further investigation or consideration in combination therapies. TRIAL REGISTRATION: Registered at the Mashhad Medical University of Medical Science: IR.MUMS.MEDICAL.REC.1402.191. The date of enrolment of the first patient into the trial is January 21, 2023. © 2025. The Author(s).

OBJECTIVES: Asprosin is a newly discovered adipokine associated with insulin resistance and diabetes mellitus. Currently, its role during gestation is under investigation, as asprosin seems to increase during pregnancy, contributing to the onset of complications, like gestational diabetes. Considering the beneficial effects of myo-inositol to support the physiological pregnancy, recovering and preventing adverse maternal and fetal outcomes, we aimed to evaluate the effects of its supplementation on serum asprosin levels in pregnant women. DESIGN: We enrolled 40 patients at the early stages of pregnancy and randomly distributed them to a study group, which received 2-g myo-inositol and 200-μg folic acid twice a day, or to a control group, which received the sole folic acid. RESULTS: After 20-22 weeks of treatment, we recorded a decrease of serum asprosin values as well as of HOMA-IR index in the group supplemented with myo-inositol, while the group that took only folic acid showed an increase in asprosin levels and no worsening of insulin resistance indices (HOMA-IR index). LIMITATIONS: The small number of patients could be a limitation of the study. CONCLUSIONS: Asprosin may be modulated by myo-inositol. This opens the possibility of considering this adipokine as a useful marker of insulin resistance to assess in pregnant women and to efficaciously target in clinical practice. Trial Registration: ClinicalTrials.gov identifier: NCT05943158.

Introduction: Polycystic ovary syndrome (PCOS) is associated with increased cardiovascular risk later in life. Insulin resistance, common in PCOS, heightens the risk of type 2 diabetes, dyslipidemia, hypertension, and cardiovascular disease. This study explored whether insulin sensitizers could modify traditional cardiovascular risk factors, through influence on insulin resistance. Objectives: To evaluate the impact of Metformin and Myoinositol therapy on glycemic and lipid profiles in PCOS patients, based on body mass index (BMI). Methods: A prospective, randomized clinical study was conducted at the UC for Endocrinology in Skopje (2022-2023). Women aged 18-40 with PCOS (Rotterdam 2003 criteria) were assigned to either Metformin (1500 mg XR) or Myoinositol (2 g + 200 mg folic acid TID) for 6 months. Parameters monitored included BMI, fasting plasma glucose (FPG), HOMA-IR, total cholesterol, LDL-C, HDL-C, triglycerides, lipid accumulation product (LAP), and TG/HDL ratio. Results: Baseline BMI significantly influenced HDL, triglycerides, TG/HDL, and LAP. Myoinositol significantly improved cholesterol regardless of BMI. Among patients with BMI ≥25 kg/m², Metformin significantly reduced FPG (4.65 ± 0.5 vs 5.01 ± 0.3 mmol/L) and HOMA-IR (2.25 ± 0.6 vs 2.94 ± 1.1 mmol/L). HOMA-IR positively correlated with TG/HDL ratio (R=0.2086, p=0.016). Conclusion: Myoinositol improved cholesterol in PCOS patients regardless of BMI. Metformin significantly affected glycemic control in overweight patients. The TG/HDL ratio may serve as a predictive marker for insulin resistance in PCOS. © 2025 Aleksandra Stevchevska et al., published by Macedonian Academy of Sciences and Arts.

Comment in JAMA. 2025 Oct 7;334(13):1147-1148. doi: 10.1001/jama.2025.14399. IMPORTANCE: Pregnant individuals with polycystic ovary syndrome (PCOS) present with a higher risk of pregnancy complications, including gestational diabetes, preeclampsia, and preterm birth. Myo-inositol supplementation may reduce these risks. OBJECTIVE: To determine whether daily supplementation with myo-inositol during pregnancy among individuals with PCOS reduces the risk of a composite outcome of gestational diabetes, preeclampsia, and preterm birth. DESIGN, SETTING, AND PARTICIPANTS: This double-blind, placebo-controlled, randomized trial was conducted at 13 hospitals in the Netherlands. Pregnant individuals with PCOS who were between 8 and 16 weeks' gestation were enrolled between June 2019 and March 2023. Final follow-up was complete on December 27, 2023. Analyses were conducted July 2024. INTERVENTIONS: Participants were randomized on a 1:1 basis to receive sachets with either myo-inositol, 2 g, with 0.2 mg of folic acid twice daily (n = 230) or matching placebo with 0.2 mg of folic acid only (n = 234) until delivery. MAIN OUTCOMES AND MEASURES: The primary outcome was a composite of gestational diabetes, preeclampsia, or preterm birth (before 37 weeks' gestation). RESULTS: Among 464 participants, the mean (SD) age was 31.5 (3.8) years; 18 participants (3.9%) reported Asian race and 395 (86.1%) reported White race. The prevalence of biochemical hyperandrogenism was higher at baseline in the myo-inositol group than the placebo group (29.0% [53 of 180] vs 18.5% [37 of 193]). A primary outcome event occurred in 25.0% (n = 56) of participants in the myo-inositol group and 26.8% (n = 61) in the placebo group (relative risk, 0.93 [95% CI, 0.68-1.28]; P = .67). CONCLUSIONS AND RELEVANCE: Myo-inositol supplementation during pregnancy did not reduce the incidence of a composite of gestational diabetes, preeclampsia, or preterm birth in patients with PCOS. TRIAL REGISTRATION: onderzoekmetmensen.nl Identifier: NL67329.078.18.

OBJECTIVES: Asprosin, a novel adipokine primarily secreted by white adipose tissue, has been implicated in the pathogenesis of insulin resistance and metabolic dysfunction. Its elevated levels characterize patients with polycystic ovary syndrome (PCOS) exhibiting metabolic alterations. Aim of this work was to evaluate the effects of insulin sensitizer administration, as inositols, on asprosin levels and then compare these results with the effects of metformin treatment. MATERIAL AND METHODS: 30 patients with PCOS were enrolled in this study and randomly divided into two groups: (i) group 1 assumed a dietary supplement based on 40:1 myo-inositol (MI)/D-chiro-inositol (DCI), (ii) group 2 assumed metformin (MET), for 12-16 weeks of treatment. RESULTS: The reduction of serum asprosin levels in patients with PCOS after treatment with MET and MI/DCI is the most intriguing result. Its levels decreased more in the inositol group, although they did not reach statistical significance probably due to the lower number of patients. CONCLUSIONS: The observed dysregulation of asprosin levels in PCOS highlights a potential link between this novel adipokine and the pathophysiology of the disorder, suggesting a modulatory effect of the combined 40:1 MI/DCI on asprosin levels. Of course, further studies may contribute to disclosing molecular mechanisms underlying asprosin reduction and open toward new perspectives.

This study investigated the effect of myo-inositol on apoptosis-related genes expression in cumulus cells of polycystic ovary syndrome (PCOS) patients undergoing intracytoplasmic sperm injection (ICSI), and its relationship with the of quality oocyte and embryo. In the study of placebo-controlled clinical trial, sixty infertile women with PCOS undergoing ICSI were randomly assigned to two groups: 1) the placebo (PLA) group obtained a placebo involving 1 mg of folic acid twice a daily for 6 weeks. 2) The MYO group obtained 2000 mg Myo-inositol + 1 mg folic acid twice a daily for the same duration, beginning concurrently with the ICSI cycle. Real-time polymerase chain reaction (real-time PCR) was used to assess the expression of Survivin, Bcl-2, Caspase-3, Caspase-7, and TNF-α in cumulus cells. Although the levels of Survivin and Bcl-2 expression were significantly increased in the MYO group compared to the placebo, levels of Caspase-3, Caspase-7, and TNF-α expression were significantly lower. A strong correlation was found between the expression levels of these genes and embryos with good quality. These findings suggest that Myo-inositol administration in PCOS patients undergoing ICSI may improve of apoptosis-related genes expression (Survivin, Bcl-2, Caspase-3, Caspase-7, and TNF-α) in cumulus cells. Nevertheless, additional expected surveys are essential to verify these results and create their clinical applicability. (Registration details: Date: 2022.10.19, Registry: https://irct.behdasht.gov.ir/trial/66005 , and Trial registration: IRCT202220921056008N1). © 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

This study aimed to evaluate the comparative efficacy of Myo-inositol (MI) and D-chiro-inositol (DCI) with metformin in enhancing ovarian function, promoting ovulation, and reducing perceived stress in patients with polycystic ovary syndrome (PCOS). Women with PCOS were identified using the Androgen Excess Society's criteria, and 60 participants were enrolled and divided equally into two groups. One group received a 40:1 ratio of MI plus DCI, while the other received metformin for a 12-week period. Endocrine and metabolic parameters, insulin-resistance, stress levels, and quality of life were assessed pre- and post-treatment. Both MI plus DCI and metformin significantly improved insulin sensitivity (HOMA-IR, p < 0.001), SHBG levels (p = 0.021), ovarian volume (p < 0.001), and menstrual regularity (p = 0.002), along with BMI, quality of life, and PSS scores (p < 0.001). Metformin showed slightly better outcomes in certain parameters, such as insulin sensitivity and endocrine markers, probably due to a higher representation of Phenotype A. In contrast, we hypothesize that MI plus DCI may be more effective for Phenotypes C and D. Our findings support both MI plus DCI and metformin as effective treatments for PCOS, with each treatment offering specific benefits. These results highlight the potential for a phenotype-specific tailored therapeutic approach to better manage the complex metabolic, endocrine, and stress-related challenges of PCOS. Trial Registration: clinicalTrial.gov NCT05767515. Registered 3 February, 2023. © 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

The research investigated the capacity of myo-inositol (MI) in order that it improves biochemical markers in serum and follicular fluid and, ultimately, intracytoplasmic sperm injection (ICSI) outcomes of women with PCOS. Sixty infertile patients with PCOS, who were undergoing ovulation induction for ICSI, were randomly divided to two groups. The MI group received 2000 mg myo-inositol + 1 mg folic acid twice a day for 6 weeks with starting the ICSI cycle. For the same period, the control group received a placebo containing only folic acid (1 mg). Levels of hormonal profiles in serum and follicular fluid, as well as oxidative stress markers (MDA, TAC, GPx, and SOD), were estimated using an ELISA assay. Primary end points were ICSI cycle outcomes. Compared to the placebo group, the MI group demonstrated significant reduction in serum and follicular fluid levels of LH, LH/FSH ratio, total testosterone, AMH, and androstenedione. Furthermore, the MI group exhibited meaningful increases in TAC, GPx, and SOD, but MDA significantly decreased. While the number of retrieved and mature oocytes is not statistically similar among the groups, the MI group showed significant improvements in the percentage of immature oocytes, cleavage rate, and good embryo quality. A meaningful correlation was checked between follicular fluid AMH level and LH, FSH, total testosterone, androstenedione, insulin, MDA, the number of retrieved oocytes, and immature oocytes. Our outcomes indicate that myo-inositol administration in women with PCOS undergoing ART helps to improve their hormonal profiles, and the quality of oocytes and embryos. Registration details: Date: 2022.10.19, Registry: https://irct.behdasht.gov.ir/trial/66005 , and Trial registration: IRCT202220921056008N1. © 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

INTRODUCTION: PCOS, beyond being characterized by reproductive disturbances, is a complicated rapid expanding metabolic and endocrinologic disorder of the recent times. Nearly 70% PCOS women show resistance to insulin. AIM: The aim of the study is to determine and compare the effectiveness of acarbose plus metformin and acarbose plus myo-inositol combination therapy in alleviating the metabolic and endocrinologic complications of PCOS. MATERIALS AND METHODS: An open labelled RCT was conducted on 168 PCOS women attending the gynaecology clinic at SRM MCH & RC, Chengalpattu and the trial was registered in CTRI (No. CTRI/2022/04/041877). Group A (n = 56) received metformin 500 mg/TID alone; group B (n = 54) received (acarbose 25 mg/TID for 4 weeks then 50 mg/TID for other 20 weeks) along with metformin 500 mg/TID and group C (n = 54) received (acarbose 25 mg/TID for 4 weeks then 50 mg/TID for other 20 weeks) along with myoinositol 1000 mg/BD. All parameters were measured at baseline and at the end of 6 months. RESULTS: Significant reduction of LH, LH: FSH, TT, HOMA-IR was observed in all the groups. FSH increased only in metformin group. Increase in serum progesterone and reduction in FI, TGL, LDL were significant only in acarbose plus myo-inositol group. SHBG and HDL increased significantly only in acarbose plus metformin group. No changes in BMI, TC and VLDL were observed in any group. CONCLUSION: Therefore, decrease in FI, HOMA-IR, TGL, LDL seen in acarbose plus myo-inositol group indirectly contributes to cardio-metabolic safety in PCOS. Similarly, a significant increase in SHBG levels with acarbose plus metformin group shows correction of the excess androgen and restoration of ovulation.

OBJECTIVE: To describe the serum anti-Müllerian hormone (AMH) concentrations in a large, well-phenotyped cohort of women with polycystic ovary syndrome (PCOS) and evaluate whether AMH predicts successful ovulation induction in women treated with clomiphene and metformin. DESIGN: Secondary analysis of randomized controlled trial. SETTING: Not applicable. PATIENT(S): A total of 333 women with anovulatory infertility attributed to PCOS who participated in the double-blind randomized trial entitled the Pregnancy in Polycystic Ovary Syndrome I (PPCOS I) study (registration number, NCT00068861) who had serum samples from baseline laboratory testing available for further serum analysis were studied. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): The association between the baseline AMH levels in each of the 3 treatment groups and ovulation, pregnancy, and live birth rates were assessed. RESULT(S): A total of 322 individuals had a baseline AMH concentration available, of which the mean AMH was 11.7 ± 8.3 ng/mL (range 0.1-43.0 ng/mL). With each unit (1 ng/mL) increase in baseline AMH, the odds of ovulation decreased by 10% (odds ratio, 0.90; 95% confidence interval, 0.86-0.93); this effect did not differ by treatment group. Women with a high baseline AMH concentration (>8 ng/mL) were significantly less likely to ovulate compared with those with a normal baseline AMH concentration (<4 ng/mL) (odds ratio, 0.23; 95% confidence interval, 0.05-0.68). This remained statistically significant when controlling for confounders, including age, body mass index, time in study, and Homeostatic Model Assessment for Insulin Resistance score. Ovulation occurred even at very high AMH concentrations; there was no maximum level noted at which no ovulation events occurred. Baseline AMH concentration was not associated with pregnancy or live birth rates when controlling for confounders. CONCLUSION(S): These AMH values in well-phenotyped individuals with PCOS add to the literature and will aid in identifying AMH criteria for the diagnosis of PCOS. In women with infertility and PCOS, a higher AMH concentration was associated with reduced odds of ovulation with ovulation induction wit

The present study was planned to evaluate the benefit of synergetic effect of Metformin plus Myo-inositol versus Metformin alone in infertile polycystic ovarian syndrome (PCOS) women undergoing ovulation induction. One hundred and twenty infertile PCOS women were randomized: Group I (n = 60) received Metformin (500 mg) plus Myoinositol(600 mg) three times a day; Group II received Metformin 500 mg three times a day. Subjects were advised to try for spontaneous conception. Those who did not conceive after 3 months, were given three cycles of ovulation induction + intrauterine insemination. Hormonal and biochemical profile parameters were done at baseline and after 3 months of therapy. Primary outcome measure was live birth rate. Secondary outcomes were improvement in menstrual cycle, hormonal and biochemical parameters, spontaneous conception, abortions, multiple pregnancy, and ovarian hyperstimulation syndrome. Baseline demographic, hormonal and biochemical parameters were comparable in two groups. There was a significant improvement in menstrual cycles (cycle length and bleeding days) in Group I as compared to Group II. The improvement in biochemical and hormonal parameters were comparable in the two groups after 3 months. Live birth rate was significantly higher in the Group I as compared to Group II [55% (33/60); 26.67% (16/60); p = .002]. The study concluded significantly higher live birth rate in women receiving the combination as compared to metformin alone.

OBJECTIVES: This umbrella review aimed to synthesize and appraise the evidence regarding the efficacy of inositol for Polycystic Ovary Syndrome (PCOS) by integrating meta-analyses of randomized controlled trials(RCTs), thereby assessing the robustness of the existing body of evidence. METHODS: We searched four databases from inception to August 2025 for relevant RCT meta-analyses. Primary outcomes included hormonal profiles, glycolipid metabolism, anthropometrics, and reproductive outcomes. Quality was assessed using AMSTAR-2 and GRADE. RESULTS: Thirteen meta-analyses were included. AMSTAR-2 ratings were 23.1% high, 53.8% low, and 23.1% very low quality. GRADE assessment of 85 evidence items revealed no high-quality evidence; 18.9% were moderate, 40% low, and 41.1% very low quality. Pooled analyses demonstrated that inositol significantly improved multiple outcomes compared to placebo/FA: it reduced serum luteinizing hormone (LH: MD -3.43 IU/L, 95% CI [-4.29, -2.56], P < 0.00001), total testosterone (TT), free testosterone (FT: MD -0.02 nmol/L, 95% CI [-0.02, -0.01], P < 0.00001), improved sex hormone-binding globulin (SHBG: MD 36.72 nmol/L, 95% CI [28.52, 44.91], P < 0.00001), and androstenedione. Benefits were also observed for homeostatic model assessment of insulin resistance (HOMA-IR: MD -1.14, 95% CI [-1.35, -0.94], P < 0.00001), fasting insulin (FI: MD -23.40 pmol/L, 95% CI [-32.80, -14.01], P < 0.00001), triglycerides, and reproductive outcomes (live births: Risk Ratio [RR] 2.29, 95% CI [1.07, 4.93], P = 0.03; ovulation rate: RR 2.75, 95% CI [1.71, 4.41], P < 0.0001). However, versus metformin(MET), its effects on most parameters were not significant, except for triglycerides and pregnancy rates. Cross-subgroup analysis of inositol subtypes indicated MI/MI+FA was superior for metabolic and reproductive outcomes, while D-chiro-inositol monotherapy should be used with caution in clinical practice; combination therapy did not consistently outperform monomers. CONCLUSION: Inositol improves core PCOS manifestations. Supported by moderate-quality evidence for effects on TT, FT, SHBG, HOMA-IR, and pregnancy/ovulation rates, it is a promising therapy. Differenti

BACKGROUND AND OBJECTIVES: Nutrient supplements are commonly used to improve fertility outcomes by women with infertility trying to conceive spontaneously or utilising medically assisted reproduction (MAR). However, despite their widespread use and perceived safety, there is a lack of clear guidance on the efficacy and safety of these supplements for female infertility. The aim of this umbrella review was to identify the best available and most recent evidence on the efficacy and safety of nutrient supplements for female infertility to provide evidence-based guidance for clinicians and reproductive couples. METHODS: Five electronic databases were searched for umbrella reviews, meta-analyses, and systematic reviews of randomised controlled trials on nutrient supplements for female infertility, published from August 2017 to January 2024. The primary outcomes were live birth, and clinical and biochemical pregnancy rates. Secondary outcomes were adverse effects including miscarriage and ectopic or multiple pregnancy. Quality assessment was performed using the A MeaSurement Tool to Assess systematic Reviews Version 2.0 (AMSTAR 2), and the certainty of evidence for outcomes were assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, where possible. RESULTS: Four meta-analyses were included. Multiple micronutrients and antioxidants increased live birth rates in women utilising MAR and/or trying to conceive spontaneously compared to placebo, standard or no treatment (odds ratio (OR) 2.59 and 1.81 respectively) with very low certainty evidence. L-carnitine, coQ10, melatonin, myo-inositol, NAC and vitamin D increased clinical pregnancy rates in women with PCOS and/or undergoing MAR compared to placebo, standard or no treatment (odds ratio (OR) 11.14, 2.49, 1.66, relative risk (RR) 1.52, OR 2.15, and 1.49 respectively) with very low certainty evidence. Vitamin D did not increase biochemical pregnancy rates in women utilising MAR with very low certainty evidence. NAC, vitamin D, and pooled antioxidants had no effect on miscarriage rates or multiple pregnancy rates in women trying to conceive spontaneously or utilising MAR, wit

PURPOSE: To compare the efficacy and safety of metformin, anti-obesity agents, and inositol with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). METHODS: A comprehensive search was conducted in PubMed, Web of Science, Embase, Cochrane Library, and ClinicalTrials.gov for studies published in English up to October 26, 2024. Randomized controlled trials (RCTs) evaluating metformin, anti-obesity agents, and inositol were included. A network meta-analysis was performed using frequency statistical methods. Subgroup analyses were conducted based on controlled ovarian stimulation (COS) protocols and body mass index(BMI). The research protocol was registered with PROSPERO (registration code CRD42024502823). RESULTS: 20 RCTs were included with 1,827 patients assessed six different agents. Nineteen trials were rated low risk, with one rated moderate risk. Pairwise meta-analysis showed that metformin did not improve pregnancy outcomes but was associated with a reduced ovarian hyperstimulation syndrome (OHSS) risk (OR = 0.52, 95% CI 0.33-0.83), particularly in agonist protocols, along with lower E2 levels on the trigger day (SMD = -0.56, 95% CI -0.90 to -0.21) and increased side effects (OR = 6.85, 95% CI 4.32-10.86). Network meta-analysis confirmed no significant differences in pregnancy outcomes for these agents compared to controls, though both myoinositol and metformin reduced OHSS risk. Myoinositol was linked to a shorter gonadotropin duration (SMD = -1.21, 95% CI -2.03 to -0.38) and fewer side effects (OR = 0.23, 95% CI 0.06-0.83) compared to controls. Metformin led to lower E2 levels, a higher number of mature oocytes, and increased side effects (SMD = -376.52, 95% CI -610.83 to -142.22; SMD = 2.23, 95% CI 0.36-4.10; OR = 6.85, 95% CI 4.32-10.86) than controls. No studies reported an increased risk of fetal abnormalities. CONCLUSION: Metformin and myoinositol may reduce OHSS risk in PCOS patients but did not significantly improve pregnancy outcomes. Metformin may lower OHSS risk in agonist protocol, reduce E2 levels on trigger day and increase mature oocytes but cause more side effects, while myoino

PURPOSE: Metformin was the first medication targeting insulin resistance in PCOS, and it has been extensively studied as a metabolic treatment option. In recent years, inositols have emerged as potential treatment options for PCOS, but confidence in the available evidence supporting their use is limited. METHODS: We comprehensively searched PubMed, Embase, and Cochrane databases for RCTs comparing the use of combined metformin and inositol versus metformin alone in women with PCOS. A random-effects model was used to calculate the risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs). A p-value of <0.05 was deemed as statistically significant. RESULTS: Six RCTs and 388 patients were included in the analysis, with follow-up ranging from 3 to 6 months. Combination therapy was significantly associated with improved menstrual cycle regularity (RR 1.56; 95% CI 1.01 to 2.41; p = 0.04), and lower values of modified Ferriman-Gallwey score (MD -0.97; 95% CI -1.53 to -0.40; p < 0.01) and LH/FSH ratios (MD -0.13; 95% CI -0.24 to -0.03; p = 0.01). Differences in acne (p = 0.58), body mass index (p = 0.13), fasting blood glucose (p = 0.07) and HOMA-IR (p = 0.25) were not statistically significant. CONCLUSION: In this meta-analysis of RCTs, combination therapy was associated with cycle regularization and reduction in hirsutism and LH/FSH ratio compared to metformin monotherapy. Further studies are needed to clarify the true benefits of the use of inositol in PCOS treatment. © 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Erratum in J Clin Endocrinol Metab. 2024 Nov 18;109(12):e2365. doi: 10.1210/clinem/dgae588. CONTEXT: Insulin resistance is common in women with polycystic ovary syndrome (PCOS). Inositol may have insulin sensitizing effects; however, its efficacy in the management of PCOS remains indeterminate. OBJECTIVE: To inform the 2023 international evidence-based guidelines in PCOS, this systematic review and meta-analysis evaluated the efficacy of inositol, alone or in combination with other therapies, in the management of PCOS. DATA SOURCES: Medline, PsycInfo, EMBASE, All EBM, and CINAHL from inception until August 2022. STUDY SELECTION: Thirty trials (n = 2230; 1093 intervention, 1137 control), with 19 pooled in meta-analyses were included. DATA EXTRACTION: Data were extracted for hormonal, metabolic, lipids, psychological, anthropometric, reproductive outcomes, and adverse effects by 1 reviewer, independently verified by a second. DATA SYNTHESIS: Thirteen comparisons were assessed, with 3 in meta-analyses. Evidence suggests benefits for myo-inositol or D-chiro-inositol (DCI) for some metabolic measures and potential benefits from DCI for ovulation, but inositol may have no effect on other outcomes. Metformin may improve waist-hip ratio and hirsutism compared to inositol, but there is likely no difference for reproductive outcomes, and the evidence is very uncertain for body mass indexI. Myo-inositol likely causes fewer gastrointestinal adverse events compared with metformin; however, these are typically mild and self-limited. CONCLUSION: The evidence supporting the use of inositol in the management of PCOS is limited and inconclusive. Clinicians and their patients should consider the uncertainty of the evidence together with individual values and preferences when engaging in shared decision-making regarding the use of inositol for PCOS. © The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.

BACKGROUND: Polycystic ovary syndrome (PCOS) treatment in adolescents currently focuses on lifestyle interventions, with pharmacological treatment options often limited to hormonal contraceptives. Several of these carry broad side-effect profiles and are not always accepted by young girls. There is growing interest in non-hormonal therapies for PCOS. We aimed to collate the evidence on the use of myoinositol or D-chiro-inositol in the improvement of PCOS symptoms in symptomatic adolescents. CONTENT: A systematic literature review identifying key articles from inception to March 2023. Participants: Female adolescents (aged 12-19 years) with PCOS or PCOS-like features. Intervention: Myoinositol or D-chiro-inositol with or without additional interventions. Comparison: Any other treatment, including lifestyle interventions, hormonal therapy, metformin or no treatment. The main outcome measure were improvement in symptoms, quality of life and adverse effects. SUMMARY: Eight studies were included: two randomised open-label trials, one quasi-randomised and three non-randomised interventional studies, one case-control study and one cohort study. All studies showed improvements in some biochemical markers, metabolic parameters or clinical symptoms, but these were not reproducible across all studies. OUTLOOK: The benefit of myoinositol in adolescents with PCOS remains unclear, with limited high-quality evidence. This review highlights the need for robustly conducted research to inform clinical practice. © 2023 Walter de Gruyter GmbH, Berlin/Boston.